Hydrogen Peroxide–Producing Lactobacilli Are Associated With Lower Levels of Vaginal Interleukin-1β, Independent of Bacterial Vaginosis

Abstract

Background The presence of hydrogen peroxide (H2O2)-producing lactobacilli in the vagina is associated with decreased rates of preterm birth and HIV acquisition. We hypothesize that this is due to immunomodulatory effects of these species. Methods Concentrations of IL1β, IL6, IL8, secretory leukocyte protease inhibitor (SLPI) and human beta defensin 2 (HBD2) were quantified from vaginal swabs from 4 groups of women: women with and without bacterial vaginosis (BV) by Nugent score, further stratified by detection of H2O2-producing lactobacilli by semi-quantitative culture. Ten quantitative PCR assays characterized presence and quantity of select Lactobacillus and BV-associated species in each group. Levels of immune markers and bacteria were compared between the four groups using ANOVA, Kruskal-Wallis, Mann Whitney U or chi-square tests. Results Swabs from 110 women from four groups were included: 26 had a normal Nugent score (BV−), and no H2O2-producing lactobacilli detected(H2O2−), 47 were BV−, H2O2+, 27 BV+, H2O2− and 10 BV+, H2O2+. The groups were similar in age, marital status and reproductive history, but not ethnicity: the BV−, H2O2− group had more Caucasian participants(p = 0.02). In women with and without BV, IL1β was lower in the H2O2+ groups. HBD2 was lowest in BV+ H2O2− women and highest in BV−, H2O2−. SLPI was lower in women with BV, and did not differ by the presence of H2O2–producing lactobacilli. In regression analysis higher quantities of L. crispatus were associated with lower quantities of IL1β. Detection and quantity of BV-associated species by qPCR was significantly different between women with and without BV, but not between women with and without H2O2-producing lactobacilli within those groups. Conclusions The presence of H2O2-producing lactobacilli is associated with lower levels of some vaginal pro-inflammatory cytokines, even in women with BV.

Association of gestational diabetes mellitus and abnormal vaginal flora with adverse pregnancy outcomes

“…Vaginal Lactobacillus produces hydrogen peroxide to regulate microecological homeostasis, thereby preventing infections from external pathogens. [ 47 , 48 ] Lamont et al [ 49 ] reported that hydrogen peroxide was generated by 100% of L crispatus , but only by 80% of L acidophilus . The present study showed that even though the constitutional ratio of L acidophilus rose in the vagina of GDM pregnant women, the ratio of L crispatus declined, which could weaken the overall production of hydrogen peroxide, thereby favoring the growth of diverse conditional pathogens.…”

The implausible “in vivo” role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota

“…The strong inverse correlation between pH and lactic acid levels indicates that lactic acid is the main acidifier in the lower FRT [ 19 ]. Lactic acid has been shown to have antimicrobial activity [ 32 , 33 ], as well as anti-inflammatory properties on cervicovaginal epithelial cells, which together support a role in lowering the risk of sexually transmitted infection acquisition and transmission [ 34 , 35 ]. In vitro and at physiological concentrations (55–111 mM) and pH (4.5), lactic acid inactivates 17 different BV-associated bacteria, while not affecting the viability of four vaginal Lactobacillus spp.…”

Barriers to a cure for HIV in women

“…In the lower female genital tract, the microbiome plays an important role in determining the risk of acquisition and transmission of a variety of diseases including sexually transmitted infections and ascending infections of the upper genital tract [ 91 ]. Colonization with hydrogen peroxide-producing Lactobacillus maintains vaginal health and is associated with a reduced inflammatory environment [ 92 ], whereas bacterial microenvironments with a great deal of species diversity (as in bacterial vaginosis) are associated with increased production of inflammatory cytokines [ 93 ], greater numbers of activated immune cells [ 94 ], and enhanced HIV RNA shedding [ 93 , 95 – 97 ].…”